Glutathione-related inhibition of prostaglandin metabolism

Placental homogenates contain a heat-stable, dialyzable fraction which specifically inhibits two placental enzymes, both of which possess 15-hydroxyprostaglandin dehydrogenase and 9-ketoprostaglandin reductase activities. The inhibition of the two enzymes is the same. The inhibitor has been resolved into two components by gel filtration on a column of Sephadex LH-20. The component which eluted first has been identified as oxidized glutathione (GSSG), the other as a glutathione-containing material (GSX). Inhibition of the 15-hydroxyprostaglandin dehydrogenase activity is competitive with respect to the prostaglandin substrate (K_i^GSSG = 26 μM, K_i^GSX = 1.4 μM). Inhibition of the 9-ketoprostaglandin reductase activity is also competitive with respect to the prostaglandin substrate (K_i^GSSG = 68 μM). The most effective inhibitor of the 15-hydroxyprostaglandin dehydrogenase is the prostaglandin A₁-glutathione adduct (K_i = 0.27 μM). This compound is not a substrate for oxidation of the 15-hydroxyl group but it is the best substrate found to date for reduction of the 9-keto function.     

Temperature dependence of binding of hyaluronate oligomer to bovine nasal proteoglycan

An ultrafiltration technique was used to study the temperature coefficient of the association constant K for 1:1 binding of proteoglycan to a hyaluronate oligosaccharide fraction containing an average of about 16 monosaccharide units. The proteoglycan was concentrated during the filtration experiment in order to provide minimal disturbance of the equilibrium in the retained solution. Analytical results calculated from assay of ³H-labeled hyaluronate in the filtrate fractions were extrapolated back to initial equilibrium cell conditions. At 10 °C values of K obtained in this way from ultrafiltration agreed within experimental error with those from equilibrium dialysis. Apparent K values obtained with both techniques tended to decrease somewhat with increasing proteoglycan concentration, due probably in part to excluded volume effects. Values of K obtained by ultrafiltration over the temperature range 5 to 40 °C were used to estimate the enthalpy of binding ΔH° as ?17.5 (±1.5) kcal mol^?1 and the entropy of binding ΔS° as ?50 (±5) cal K^?1 mol^?1 (based on a 1 μm standard state). The dilute solution value of K at 37 °C is sufficiently large to suggest that most of the proteoglycan monomers having a binding site are complexed under tissue conditions.     

Chromosome Interactions in DROSOPHILA MELANOGASTER. II. Total Fitness

In a large experiment, using nearly 200 population cages, we have measured the fitness of Drosophila melanogaster homozygous (1) for the second chromosome, (2) for the third chromosome, and (3) for both chromosomes. Twentyfour second chromosomes and 24 third chromosomes sampled from a natural population were tested. The mean fitness of the homozygous flies is 0.081 ± 0.014 for the second chromosome, 0.080 ± 0.017 for the third chromosome, and 0.079 ± 0.024 for both chromosomes simultaneously. Assuming that fitnesses are multiplicative (the additive fitness model makes no sense in the present case because of the large selection coefficients involved), the expected mean fitness of the homozygotes for both chromosomes is 0.0066; their observed fitness is more than ten times greater. Thus, it appears that synergistic interactions between loci are considerable; and that, consequently, the fitness function substantially departs from linearity. Two models are tentatively suggested for the fitness function: a "threshold" model and a "synergistic" model.—The experiments reported here confirm previous results showing that the concealed genetic load present in natural populations of Drosophila is sufficient to account for the selective maintenance of numerous polymorphisms (of the order of 1000).     

Organization and Evolution of the Mammalian Genome: I. Polymorphism of H-2 Linked Loci

To test the hypothesis that the H-2 polymorphism is adaptive, the degree of polymorphism of loci linked to the H-2 complex on chromosome 17 of the house mouse was compared to the degree of polymorphism of loci located on other chromosomes. Published theoretical analyses show that polymorphisms subject to natural selection usually reduce the polymorphism of linked neutral loci. The first test of the hypothesis was based on data obtained from a survey of the polymorphism of 12 isozyme-encoding loci in wild house mice from Europe, North Africa and South America. Results of this test showed that, on the average, H-2-linked loci were as polymorphic as loci located on other chromosomes. In fact, the data suggested that H-2 linked loci might be more polymorphic than other loci. To test this hypothesis more rigorously, data for the 12 isozyme-encoding loci were augmented with data from published surveys of the polymorphisms of 59 loci in house mice from Europe and North America. Results of these tests showed that polymorphic loci linked to the H-2 complex tended to be more, rather than less, polymorphic than loci located on other chromosomes. The cluster of highly polymorphic loci seems to be related to linkage of these loci to the highly polymorphic H-2 complex, but the way in which the influence is exerted could not be readily explained.     

Estimation of Genetic Variability in Natural Populations of DROSOPHILA SIMULANS by Two-Dimensional and Starch Gel Electrophoresis

Genic variation in natural populations of Drosophila simulans was surveyed using allozymic and two-dimensional electrophoretic techniques. Consistent with some previous reports, allozymic heterozygosity appeared lower than in the sibling species D. melanogaster (0.07 vs. 0.16). No variation was detected by two-dimensional electrophoresis of 19 lines scored for 70 abundant proteins. This is consistent with reported reductions in estimates of genic heterozygosity by two-dimensional electrophoresis in D. melanogaster, Mus musculus, and man. Although the amount of intraspecific variation detected in abundant proteins was lower than that detected for allozymes in D. simulans and D. melanogaster, the genetic distances between the sibling species calculated from the two data sets are not significantly different (0.35 and 0.20). The allozyme and two-dimensional electrophoresis data confirmed the impression from other measures of genetic variation (mitochondrial DNA restriction maps and inversion polymorphisms) that D. simulans is substantially less variable than D. melanogaster.     

A regression analysis of the summer population dynamics of Polyarthra vulgaris in a northern Michigan bog lake

The population dynamics of a planktonic rotifer (Polyarthra vulgaris) were examined in a brown water, acid lake in northern Michigan, U.S.A. Predation by Chaoborus punctipennis and low food (Navicula spp. and Cyclotella spp.) concentrations were the main factors limiting P. vulgaris populations of all factors examined. The data presented here support a hypothesis for zooplankton limitation by an invertebrate predator.     

The latex agglutination test versus counterimmunoelectrophoresis for rapid diagnosis of bacterial meningitis

A modified latex agglutination (LA) test was compared with Gram-staining and counterimmunoelectrophoresis (CIE) for the rapid detection in the cerebrospinal fluid (CSF) of antigen to Haemophilus influenzae type b, Neisseria meningitidis groups A, B and C, Escherichia coli K1, Streptococcus pneumoniae and group B streptococci, seven frequent causes of bacterial meningitis in children. Of 50 CSF samples from patients with culture-proven bacterial meningitis 90% were correctly shown by the LA test to contain antigen of the responsible organism. Gram-staining revealed organisms in 80% of 45 of these samples. In 75% of the 40 samples that were of sufficient volume for CIE, positive results for the appropriate antigen were obtained. The concentration of antigen detected in the CSF by the LA test varied from undetectable to 800 000 ng/ml. Patients with a high concentration (more than 2000 ng/ml or a positive result at dilutions of CSF over 1/8) were significantly more likely to have a poor response to therapy (two died and two had persistent pleocytosis or bacteria in the CSF) than patients with a lower concentration (4/16 v. 0/18, P < 0.05). After appropriate therapy was begun the concentration of antigen fell dramatically, but measurable amounts of antigen persisted in the CSF for up to 6 days. The LA test detected bacterial antigen at concentrations 2 to 70 times below the lower limit detected by CIE. In seven additional patients who had received antibiotics before lumbar puncture was performed the LA test detected antigen from meningitis-causing bacteria even though cultures of the CSF were sterile. In another 145 patients who did not have meningitis the results of the LA test were negative. The LA test, done as described in this article, is easier to perform than CIE and should be a useful addition to the diagnostic tests carried out on the CSF of any patient suspected of having meningitis.     

Seasonal variation in mother-daughter groupings in Siberian ibex (Capra ibex siberica)

The association of three pairs of mother-yearling Siberian ibex was recorded by noting the distance between the mothers and daughters at 5-min intervals for 1–2-h observation periods for 1 yr at the Brookfield Zoo. Monthly averages of climatological data were obtained. All three pairs showed a seasonal fluctuation of association, with a higher level during spring and fall-winter and a low degree of sociality in midsummer and late winter. Within the high social periods, short 1–3-wk periods of low association occurred, which were correlated to actual rut and calving times in individual females. The mother-daughter associations were most highly correlated to day length and sunrise of the climatological measures. These data seem to support the original hypothesis that these social periods, which began as developmental associations in the infant, aid in keeping the matrifocal herd structure together despite aggression at the times of rut and calving. It seems also that the social cycling, although linked to reproductive cycling, has its own physiological mechanism.